PMID- 31874646
OWN - NLM
STAT- MEDLINE
DCOM- 20200507
LR  - 20210327
IS  - 1471-2164 (Electronic)
IS  - 1471-2164 (Linking)
VI  - 20
IP  - Suppl 9
DP  - 2019 Dec 24
TI  - Identification of highly conserved, serotype-specific dengue virus sequences: 
      implications for vaccine design.
PG  - 921
LID - 10.1186/s12864-019-6311-z [doi]
LID - 921
AB  - BACKGROUND: The sequence diversity of dengue virus (DENV) is one of the 
      challenges in developing an effective vaccine against the virus. Highly 
      conserved, serotype-specific (HCSS), immune-relevant DENV sequences are 
      attractive candidates for vaccine design, and represent an alternative to the 
      approach of selecting pan-DENV conserved sequences. The former aims to limit the 
      number of possible cross-reactive epitope variants in the population, while the 
      latter aims to limit the cross-reactivity between the serotypes to favour a 
      serotype-specific response. Herein, we performed a large-scale systematic study 
      to map and characterise HCSS sequences in the DENV proteome. METHODS: All 
      reported DENV protein sequence data for each serotype was retrieved from the NCBI 
      Entrez Protein (nr) Database (txid: 12637). The downloaded sequences were then 
      separated according to the individual serotype proteins by use of BLASTp search, 
      and subsequently removed for duplicates and co-aligned across the serotypes. 
      Shannon's entropy and mutual information (MI) analyses, by use of AVANA, were 
      performed to measure the diversity within and between the serotype proteins to 
      identify HCSS nonamers. The sequences were evaluated for the presence of 
      promiscuous T-cell epitopes by use of NetCTLpan 1.1 and NetMHCIIpan 3.2 server 
      for human leukocyte antigen (HLA) class I and class II supertypes, respectively. 
      The predicted epitopes were matched to reported epitopes in the Immune Epitope 
      Database. RESULTS: A total of 2321 nonamers met the HCSS selection criteria of 
      entropy < 0.25 and MI > 0.8. Concatenating these resulted in a total of 337 HCSS 
      sequences. DENV4 had the most number of HCSS nonamers; NS5, NS3 and E proteins 
      had among the highest, with none in the C and only one in prM. The HCSS sequences 
      were immune-relevant; 87 HCSS sequences were both reported T-cell 
      epitopes/ligands in human and predicted epitopes, supporting the accuracy of the 
      predictions. A number of the HCSS clustered as immunological hotspots and 
      exhibited putative promiscuity beyond a single HLA supertype. The HCSS sequences 
      represented, on average, ~ 40% of the proteome length for each serotype; more 
      than double of pan-DENV sequences (conserved across the four serotypes), and thus 
      offer a larger choice of sequences for vaccine target selection. HCSS sequences 
      of a given serotype showed significant amino acid difference to all the variants 
      of the other serotypes, supporting the notion of serotype-specificity. 
      CONCLUSION: This work provides a catalogue of HCSS sequences in the DENV 
      proteome, as candidates for vaccine target selection. The methodology described 
      herein provides a framework for similar application to other pathogens.
FAU - Chong, Li Chuin
AU  - Chong LC
AD  - Centre for Bioinformatics, School of Data Sciences, Perdana University, Jalan 
      MAEPS Perdana, 43400, Serdang, Selangor Darul Ehsan, Malaysia.
FAU - Khan, Asif M
AU  - Khan AM
AUID- ORCID: 0000-0001-9202-279X
AD  - Centre for Bioinformatics, School of Data Sciences, Perdana University, Jalan 
      MAEPS Perdana, 43400, Serdang, Selangor Darul Ehsan, Malaysia. 
      asif@perdanauniversity.edu.my.
LA  - eng
PT  - Journal Article
DEP - 20191224
PL  - England
TA  - BMC Genomics
JT  - BMC genomics
JID - 100965258
RN  - 0 (Dengue Vaccines)
RN  - 0 (Epitopes, T-Lymphocyte)
RN  - 0 (Proteome)
RN  - 0 (Viral Proteins)
SB  - IM
EIN - BMC Genomics. 2021 Mar 26;22(1):219. PMID: 33771112
MH  - Amino Acid Sequence
MH  - Conserved Sequence
MH  - Databases, Protein
MH  - Dengue Vaccines/immunology
MH  - Dengue Virus/*immunology
MH  - Epitopes, T-Lymphocyte/chemistry
MH  - Evolution, Molecular
MH  - Proteome
MH  - Serogroup
MH  - Viral Proteins/*chemistry/*immunology
PMC - PMC6929274
OTO - NOTNLM
OT  - Cross-reactivity
OT  - Dengue virus
OT  - Entropy
OT  - Immune targets
OT  - Mutual information
OT  - Sequence conservation
OT  - Serotype-specific
OT  - Vaccine design
COIS- The authors have declared that no competing interests exist.
EDAT- 2019/12/26 06:00
MHDA- 2020/05/08 06:00
PMCR- 2019/12/24
CRDT- 2019/12/26 06:00
PHST- 2019/11/12 00:00 [received]
PHST- 2019/11/19 00:00 [accepted]
PHST- 2019/12/26 06:00 [entrez]
PHST- 2019/12/26 06:00 [pubmed]
PHST- 2020/05/08 06:00 [medline]
PHST- 2019/12/24 00:00 [pmc-release]
AID - 10.1186/s12864-019-6311-z [pii]
AID - 6311 [pii]
AID - 10.1186/s12864-019-6311-z [doi]
PST - epublish
SO  - BMC Genomics. 2019 Dec 24;20(Suppl 9):921. doi: 10.1186/s12864-019-6311-z.